Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea.
JAMA Psychiatry. 2014 Apr;71(4):412-22. doi: 10.1001/jamapsychiatry.2013.4506.
Cerebrovascular disease (CVD) and Alzheimer disease are significant causes of cognitive impairment in the elderly. However, few studies have evaluated the relationship between CVD and β-amyloid burden in living humans or their synergistic effects on cognition. Thus, there is a need for better understanding of mild cognitive impairment (MCI) before clinical deterioration begins.
To determine the synergistic effects of β-amyloid burden and CVD on cognition in patients with subcortical vascular MCI (svMCI).
DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study was conducted using a hospital-based sample at a tertiary referral center. We prospectively recruited 95 patients with svMCI; 67 of these individuals participated in the study. Forty-five patients with amnestic MCI (aMCI) were group matched with those with svMCI by the Clinical Dementia Rating Scale Sum of Boxes.
We measured β-amyloid burden using positron emission tomography with carbon 11-labeled Pittsburgh Compound B (PiB). Cerebrovascular disease was quantified as white matter hyperintensity volume detected by magnetic resonance imaging fluid-attenuated inversion recovery. Detailed neuropsychological tests were performed to determine the level of patients' cognitive impairment.
On evaluation, 22 of the svMCI group (33%) and 28 of the aMCI group (62%) were found to be PiB positive. The mean PiB retention ratio was lower in patients with svMCI than in those with aMCI. In svMCI, the PiB retention ratio was associated with cognitive impairments in multiple domains, including language, visuospatial, memory, and frontal executive functions, but was associated only with memory dysfunction in aMCI. A significant interaction between PiB retention ratio and white matter hyperintensity volume was found to affect visuospatial function in patients with svMCI.
Most patients with svMCI do not exhibit substantial amyloid burden, and CVD does not increase β-amyloid burden as measured by amyloid imaging. However, in patients with svMCI, amyloid burden and white matter hyperintensity act synergistically to impair visuospatial function. Therefore, our findings highlight the need for accurate biomarkers, including neuroimaging tools, for early diagnosis and the need to relate these biomarkers to cognitive measurements for effective use in the clinical setting.
脑血管疾病（CVD）和阿尔茨海默病是老年人认知障碍的重要原因。然而，很少有研究评估 CVD 与活人体内β-淀粉样蛋白负担之间的关系，以及它们对认知的协同作用。因此，在临床恶化之前，需要更好地了解轻度认知障碍（MCI）。
确定皮质下血管性 MCI（svMCI）患者中β-淀粉样蛋白负担与 CVD 对认知的协同作用。
设计、地点和参与者：一项横断面研究在三级转诊中心的医院进行。我们前瞻性地招募了 95 名 svMCI 患者；其中 67 名患者参与了这项研究。45 名有记忆障碍的 MCI（aMCI）患者与 svMCI 患者通过临床痴呆评定量表的总箱数进行组间匹配。
我们使用碳 11 标记的匹兹堡化合物 B（PiB）的正电子发射断层扫描测量β-淀粉样蛋白负担。通过磁共振成像液体衰减反转恢复检测到的脑白质高信号体积来量化脑血管疾病。进行详细的神经心理学测试以确定患者认知障碍的程度。
在评估时，svMCI 组中有 22 名（33%）和 aMCI 组中有 28 名（62%）患者被发现 PiB 阳性。svMCI 患者的 PiB 保留率低于 aMCI 患者。在 svMCI 中，PiB 保留率与包括语言、视空间、记忆和额叶执行功能在内的多个认知领域的认知障碍相关，但仅与 aMCI 中的记忆功能障碍相关。发现 PiB 保留率与脑白质高信号体积之间存在显著的相互作用，这会影响 svMCI 患者的视空间功能。
大多数 svMCI 患者没有明显的淀粉样蛋白负担，CVD 不会通过淀粉样蛋白成像增加β-淀粉样蛋白负担。然而，在 svMCI 患者中，淀粉样蛋白负担和脑白质高信号协同作用损害视空间功能。因此，我们的研究结果强调需要准确的生物标志物，包括神经影像学工具，用于早期诊断，并需要将这些生物标志物与认知测量结果相关联，以便在临床环境中有效使用。
